Abnormal expression of insulin-like growth factor-I receptor in hepatoma tissue and its inhibition to promote apoptosis of tumor cells.

Abstract

Abnormal signaling of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma, but the underlying molecular mechanisms remain largely unknown. The objective of this study was to investigate IGF-IR's role as a signaling molecule, its pathological alteration in hepatoma tissues, and its effect on hepatoma cell proliferation when inhibited. As measured by immunohistochemical analysis, the incidence of hepatic IGF-IR expression in cancerous tissue was 80.0 % (24 of 30), which was significantly higher (P < 0.05) than 43.3 % (13 of 30) occurrence in the surrounding tissue and the nondetectable (0 of 30) frequency in the distal cancerous tissue. Hepatoma IGF-IR expression was correlated to the differentiation degree and not to the number or size of tumors, HBV infection, and AFP level. The in vitro IGF-IR expression in hepatoma cells was down-regulated significantly by picropodophyllin, a specific kinase inhibitor, in a time- and dose-dependent manner. Cell proliferation was inhibited through typical mechanisms of promoting apoptosis and cell cycle arrest (G2/M phase). Up-regulation of IGF-IR in hepatocarcinogenesis suggests that the down-regulation of IGF-IR expression could be a specific molecular target for hepatoma cell proliferation.

• Authors: Zhizhen Dong, Min Yao, Li Wang, Xiaodi Yan, Xing Gu, Yun Shi, Ninghua Yao, Liwei Qiu, Wei Wu, Dengfu Yao
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 6 Pg. 3397-405 (Dec 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23797814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• picropodophyllin
• Receptor, IGF Type 1
• Podophyllotoxin

Topics

• Adult
• Aged
• Apoptosis (drug effects, genetics)
• Base Sequence
• Blotting, Western
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Female
• G2 Phase Cell Cycle Checkpoints (drug effects, genetics)
• Gene Expression Regulation, Neoplastic
• Hep G2 Cells
• Humans
• Immunohistochemistry
• Liver (metabolism, pathology)
• Liver Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Molecular Sequence Data
• Podophyllotoxin (analogs & derivatives, pharmacology)
• Receptor, IGF Type 1 (antagonists & inhibitors, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors